Human Molecular Genetics, 2001, Vol. 10, No. 17 1793-1805
© 2001 Oxford University Press
Insights into psoriasis and other inflammatory diseases from large-scale gene expression studies
1Department of Internal Medicine and 2Departments of Genetics and Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA, 3Naval Medical Research Center, Georgetown University, Kensington, MD 20895, USA and 4Department of Internal Medicine, Division of Dermatology, Baylor University Medical Center, Dallas, TX 75246, USA
Approximately 2% of the Caucasian population is affected by psoriasis (PS); a chronic inflammatory skin disease triggered by both genetic and environmental risk factors. In addition to a major contribution from the HLA class I region, PS susceptibility loci have been mapped to a number of regions including 1q21, 3q21, 4qter, 14q31–q32, 17q24–q25, 19p13.3 and 20p. Some of these overlap with loci implicated in other autoimmune/inflammatory diseases. Global gene expression studies are beginning to provide insights into the etiology of these and other complex diseases. We used Affymetrix oligonucleotide arrays comprising approximately 12 000 known genes to initiate a more comprehensive analysis of the transcriptional changes that occur in involved and uninvolved skin of 15 psoriatic patients versus six normal controls. Expression levels of the transcripts detected on the arrays were first used to determine the relationship of samples to each other using hierarchical clustering. This analysis clearly differentiated involved psoriatic skin from uninvolved and normal skin. Clusters of differentially expressed genes with similar expression patterns in the same samples were then identified. Six out of 32 clusters contained a total of 177 transcripts that were differentially expressed in involved psoriatic skin versus normal skin. These differences were independent of the gender, age, skin site and HLA class I status of the patient. Ten of the 177 genes were also differentially expressed in uninvolved skin, and several mapped to regions previously shown to harbor psoriasis susceptibility loci.
+ To whom correspondence should be addressed at: Washington University, 4566 Scott Avenue, Box 8232, St Louis, MO 63110, USA. Tel: +1 314 747 3264; Fax: +1 314 747 2489; Email: bowcock@genetics.wustl.edu
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